Paclitaxel (taxol) is a well known chemotherapeutic agent having efficacy against a broad range of cancers. It has been shown to be clinically effective against ovarian and breast cancer, and has exhibited promising activity against a number of other types of cancers such as liver, peritoneal, cervical, prostate, colon and esophageal.
Conventionally, taxol is obtained by extraction from the bark of the Pacific Taxus brevifolia. However, the isolation of taxol from the tree bark is a difficult, low-yield and expensive process. Further, the scarcity of the yew has prompted, scientists to explore alternate routes.
Although paclitaxel is a promising drug for the treatment of ovarian and breast cancers, the low water solubility of paclitaxel can be problematic. In a quest for new derivatives with potentially enhanced solubility, one of the sites on the molecule where attention has been directed is the ketone function at the C-9 position, or conversion at the C-10 acetate group on the taxane nucleus to a hydroxyl group.
Previous attempts to improve water solubility have also relied on the preparation of water soluble pro-drugs, which are converted to paclitaxel under physiological conditions, or novel drug formulations.
An alternative method of increasing water solubility of palitaxel would be to replace one of the hydroxyl groups with an amino group; salts of the resulting amine would have improved water solubility.
In the search for alternative solutions, the discovery of new taxol derivatives having broader spectrum, enhanced in vivo activity and improved water solubility and stability have been reported. Among the compounds reported, those belonging to the 9-dihydrotaxane family show great promise. Thus far, only limited members of that family, including 9-dihydrotaxol and 9-dihydrotaxotere, have been successfully synthesized. The ability to synthesize a greater number of 9-dihydrotaxane compounds having superior pharmacologic properties would be a valuable asset.